The mechanisms underlying the triggers and maintenance of atrial fibrillation (AF) are not fully understood. One potential unproved mechanism is that gastroesophageal reflux disease (GERD), in which acid reflux induces local and systemic inflammation, may increase triggered activity in the myocardium and pulmonary veins and increase AF risk. A self-report questionnaire was mailed to a random sample of 5,288 residents of Olmsted County, Minnesota, aged 25 to 74 years to assess the presence and frequency of GERD from 1988 to 1994. The long-term risk for AF over a period of 11.4 +/- 5.0 years was determined through review of clinical evaluations and the electrocardiographic database in those without previous AF. The average age was 53 +/- 17 years, and 2,571 subjects (49%) were man. Of these patients, 741 developed AF (cumulative probability of AF at 18 years 20%, 95% confidence interval [CI] 17% to 22%). Age (hazard ratio [HR] 1.09, 95% CI 1.08 to 1.10, p <0.001), male gender (HR 1.81, 95% CI 1.53 to 2.14, p <0.001), hypertension (HR 1.36, 95% CI 1.14 to 1.61, p = 0.0006), and heart failure (HR 1.74, 95% CI 1.16 to 2.60, p = 0.007) were independently associated with the risk of AF. The presence of any GERD was not associated with risk for AF (HR 0.81, 95% CI 0.68 to 0.96, p = 0.014) after adjustment for other risk factors. The frequency of GERD did not significantly affect the risk for AF, although patients with more frequent GERD had a slightly higher AF risk. Esophagitis increased the risk for AF (HR 1.94, 95% CI 1.35 to 2.78, p <0.001), but the association did not persist when accounting for other risk factors (p = 0.72). In conclusion, in this large population-based study of patients surveyed for GERD, no association was found with the presence or frequency of symptoms and AF. Patients with esophagitis were more likely to develop AF, although this association requires further study.